title: Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice.
abstract: BACKGROUND
  Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted dengue virus 3 (DENV-3) genotype I.
  
  
  METHODS
  C57BL/6 mice received 4×10(3) PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the virus in brain tissue.
  
  
  RESULTS
  All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN-γ, TNF-α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4+ and CD8+ T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain.
  
  
  CONCLUSIONS
  Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice.
authors.affiliation: Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas (ICB), UFMG, Belo Horizonte, Brazil.
authors.forename: Debora C G
authors.initials: DC
authors.lastname: Amaral
authors.forename: Milene A
authors.initials: MA
authors.lastname: Rachid
authors.forename: Marcia C
authors.initials: MC
authors.lastname: Vilela
authors.forename: Roberta D L
authors.initials: RD
authors.lastname: Campos
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Ferreira
authors.forename: David H
authors.initials: DH
authors.lastname: Rodrigues
authors.forename: Norinne
authors.initials: N
authors.lastname: Lacerda-Queiroz
authors.forename: Aline S
authors.initials: AS
authors.lastname: Miranda
authors.forename: Vivian V
authors.initials: VV
authors.lastname: Costa
authors.forename: Marco A
authors.initials: MA
authors.lastname: Campos
authors.forename: Erna G
authors.initials: EG
authors.lastname: Kroon
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003715:Dengue / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008590:Meningoencephalitis / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology* / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015996:Survival Rate